CN117777002A - An asymmetric synthesis method of 3,3-disubstituted oxyindole derivatives - Google Patents
An asymmetric synthesis method of 3,3-disubstituted oxyindole derivatives Download PDFInfo
- Publication number
- CN117777002A CN117777002A CN202311649212.8A CN202311649212A CN117777002A CN 117777002 A CN117777002 A CN 117777002A CN 202311649212 A CN202311649212 A CN 202311649212A CN 117777002 A CN117777002 A CN 117777002A
- Authority
- CN
- China
- Prior art keywords
- disubstituted
- compound
- synthesis method
- asymmetric synthesis
- reaction
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Indole Compounds (AREA)
Abstract
本发明公开了一种3,3‑二取代氧化吲哚衍生物的不对称合成方法，属于有机合成的技术领域。该方法包括以下步骤：在反应器中，在惰性氛围下，3‑取代氧化吲哚化合物在手性配体与酸催化下，与4‑己烯‑3‑酮加热反应，反应结束后进行后续分离提纯，即可得到3,3‑二取代氧化吲哚衍生物。本发明的方法步骤简单、操作安全，所用原料无毒且易得，整个过程简单易行，污染小，符合绿色化学的理念。
The invention discloses an asymmetric synthesis method of a 3,3-disubstituted oxidized indole derivative, and belongs to the technical field of organic synthesis. The method comprises the following steps: in a reactor, under an inert atmosphere, a 3-substituted oxidized indole compound is heated and reacted with 4-hexene-3-ketone under a chiral ligand and acid catalysis, and subsequent separation and purification are performed after the reaction is completed to obtain a 3,3-disubstituted oxidized indole derivative. The method of the invention has simple steps, safe operation, non-toxic and easily available raw materials, a simple and easy process, low pollution, and is in line with the concept of green chemistry.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to an asymmetric synthesis method of a 3, 3-disubstituted oxindole derivative.
Background
3, 3-disubstituted oxindole backbone structures, with quaternary chiral centers at the C3-position, are widely found in various biologically and pharmaceutically active natural products and are often used as synthetic raw materials for indole alkaloids (J.J.Badillo, N.V.Hanhan, A.K.Franz, curr.Opin.Drug discovery.level.2010, 13,758). Starting from this class of compounds, various indole alkaloids with various biological activities, such as peganimine A, carborisidine, akuamminine, vindoline, strotamine, etc., can be synthesized. More importantly, the chiral isomer may show distinct pharmacological, pharmacokinetic, metabolic and toxicological activities and the like in organisms, so that the synthesis of the optically pure 3, 3-disubstituted oxindole compound has very important significance. In 2009, the task group of Maruoka (He.R.; ding C.; maruoka K. Angewandte Chemie International Edition,2009,48,4559-4561.) reported a method for synthesizing 3, 3-disubstituted oxindole derivatives by catalyzing the reaction of 3-aryloxindoles with α, β -unsaturated ketones using chiral quaternary tetraalkylphosphonium salts as phase transfer catalysts, but the 3-substituent of the indole synthesized by this method is aryl, which limits further structural modifications to a large extent. In 2015, the phyllostane group (Wei Y.; wen S.; liu Z.; et al organic Letters,2015,17,2732-2735.) reported a method for synthesizing 3, 3-disubstituted oxindole derivatives by reacting 3-methylindole with α, β -unsaturated ketones, but the 3-substituent of indole synthesized by this method was mostly methyl, and was not well compatible with 3-functionalized alkyl substituted oxindole substrates.
In view of the diversity of natural products and drug molecules, the development of a new asymmetric synthesis method for 3, 3-disubstituted oxindole derivatives remains an important research direction.
Disclosure of Invention
In order to solve the defects and the shortcomings existing in the prior art, the invention aims to provide an asymmetric synthesis method of a 3, 3-disubstituted oxindole derivative.
The method is realized by the following technical scheme:
an asymmetric synthesis method of a 3, 3-disubstituted oxindole derivative comprises the following steps:
(1) In a reactor, under an inert atmosphere, dissolving chiral ligand and acid in an organic solvent, sequentially adding 4-hexene-3-ketone and a compound 1, and heating for reaction;
(2) After the reaction is finished, cooling to room temperature, and separating and purifying the reaction liquid to obtain the 3, 3-disubstituted oxindole derivative.
The structural formula of the compound 1 is as follows:bn is benzyl.
Further, the inert atmosphere in the step (1) is a nitrogen environment.
Further, the organic solvent in the step (1) is toluene.
Further, the acid in the step (1) is more than one of Boc-D-phenylglycine, benzoic acid, p-toluenesulfonic acid, acetic acid, N-Boc-L-proline, boc-D-phenylglycine, D-tartaric acid and L-tartaric acid.
Further, the structural formula of the chiral ligand in the step (1) is any one of the following:
further, the temperature of the heating reaction in the step (1) is 60-80 ℃, and the reaction time is 24-72 h.
Further, the molar ratio of the compound 1 to the 4-hexene-3-ketone in the step (1) is 1 (1.2-3).
Further, the molar ratio of the compound 1 to the chiral ligand in the step (1) is 1 (0.05-0.5); preferably, the molar ratio of compound 1 to chiral ligand is 1 (0.4-0.6).
Further, the molar ratio of the compound 1 to the acid in the step (1) is 1 (0.1-1).
Further, the separation and purification in the step (2) are as follows: the saturated sodium bicarbonate aqueous solution is quenched, extracted by ethyl acetate, backwashed by saturated sodium chloride solution, dried by anhydrous sodium sulfate, filtered, and the organic phase is concentrated and separated and purified by column chromatography.
Further, 3-disubstituted oxindole derivatives obtained after the reaction, including the compound 2-1 ((S) -3- (2- (dibenzylamino) ethyl) -3- ((R) -4-oxohexan-2-yl) endolin-2-one) and the compound 2-2 ((R) -3- (2- (dibenzylamino) ethyl) -3- ((R) -4-oxohexan-2-yl) endolin-2-one), have the structural formulas:
wherein Bn is benzyl and Me is methyl.
The reaction equation of the synthesis method of the invention is as follows:
compared with the prior art, the invention has the following advantages:
(1) The invention uses tryptamine derivative as raw material, which is nontoxic, cheap and easy to obtain, simple in synthesis steps and safe in operation.
(2) The 3, 3-disubstituted oxindole derivatives synthesized according to the invention contain two consecutive chiral centers and are all necessary in the corresponding natural products. Derivatization with various functional group transformations and cyclization reactions can further occur.
(3) The invention can realize the asymmetric synthesis of 3, 3-disubstituted oxindole derivatives by adding chiral ligand, and can obtain optically pure oxindole derivatives, which has important roles in the synthesis of medicines and natural products.
Drawings
FIG. 1 is a hydrogen spectrum of compound 1 of the present invention;
FIG. 2 is a carbon spectrum of compound 1 of the present invention;
FIG. 3 is a hydrogen spectrum of compound 2-1 and compound 2-2 of the present invention;
FIG. 4 is a hydrogen spectrum of compound 3-1;
FIG. 5 is a hydrogen spectrum of Compound 3-2.
Detailed Description
The invention is further described below with reference to specific examples and figures, but embodiments of the invention are not limited thereto.
Example 1
The synthesis method for asymmetrically synthesizing the 3, 3-disubstituted oxindole derivative comprises the following steps:
ligand L1 (6.0 mg,0.02 mmol) and Boc-D-phenylglycine (10 mg,0.04 mmol) were weighed into a 4mL reaction flask, anhydrous toluene (0.5 mL) was added, stirred for 10 minutes until fully dissolved, then 4-hexen-3-one (29.4 mg,0.3 mmol) was added to the reaction flask, stirred for 10 minutes until fully dissolved, then Compound 1 (35.6 mg,0.1 mmol) was weighed into the system and stirred until fully dissolved. The temperature is raised to 70 ℃ and the reaction is carried out for 72 hours. Cooling to room temperature, quenching the reaction with saturated sodium bicarbonate aqueous solution, extracting ethyl acetate until the aqueous phase has no fluorescent spots, combining all ethyl acetate phases, backwashing with saturated saline solution, drying with anhydrous sodium sulfate, filtering, and concentrating. The concentrate was purified by thin layer chromatography (petroleum ether/ethyl acetate=5:1) to give a mixture of compound 2-1 and compound 2-2 (yellow solid, 28mg, total yield: 64%, ee% (enantiomeric excess): 56%,41%; dr (diastereomeric excess): 1:1.6).
The synthetic route is as follows:
HPLC conditions: INC column (n-hexane/isopropanol=95/5, flow rate 1.0 ml/min), retention time: compounds 2-1:t R =24.4 min (main), t R =50.7 min (times); compound 2-2: t is t R =15.0 min (times), t R =27.1 min (master).
Example 2
The synthesis method for asymmetrically synthesizing the 3, 3-disubstituted oxindole derivative comprises the following steps:
ligand L1 (6.0 mg,0.02 mmol) and Boc-D-phenylglycine (10 mg,0.04 mmol) were weighed into a 4mL reaction flask, anhydrous toluene (0.5 mL) was added, stirred for 10 minutes until fully dissolved, then 4-hexen-3-one (29.4 mg,0.3 mmol) was added to the reaction flask, stirred for 10 minutes until fully dissolved, then Compound 1 (35.6 mg,0.1 mmol) was weighed into the system and stirred until fully dissolved. The temperature is raised to 80 ℃ to react for 72 hours. Cooling to room temperature, quenching the reaction with saturated sodium bicarbonate aqueous solution, extracting ethyl acetate until the aqueous phase has no fluorescent spots, combining all ethyl acetate phases, backwashing with saturated saline solution, drying with anhydrous sodium sulfate, filtering, and concentrating. The concentrate was purified by thin layer chromatography (petroleum ether/ethyl acetate=5:1) to give a mixture of compound 2-1 and compound 2-2 (yellow solid, 26.8mg, total yield: 60%, ee% (enantiomeric excess): 43%,31%; dr (diastereomeric excess): 1:1.7)
The synthetic route is as follows:
HPLC conditions: INC column (n-hexane/isopropanol=95/5, flow rate 1.0 ml/min), retention time: compounds 2-1:t R =24.4 min (main), t R =50.7 min (times); compound 2-2: t is t R =15.0 min (times), t R =27.1 min (master).
Example 3
The synthesis method for asymmetrically synthesizing the 3, 3-disubstituted oxindole derivative comprises the following steps:
ligand L2 (6.4 mg,0.02 mmol) and Boc-D-phenylglycine (10 mg,0.04 mmol) were weighed into a 4mL reaction flask, anhydrous toluene (0.5 mL) was added, stirred for 10 minutes until fully dissolved, then 4-hexen-3-one (29.4 mg,0.3 mmol) was added to the reaction flask, stirred for 10 minutes until fully dissolved, then Compound 1 (35.6 mg,0.1 mmol) was weighed into the system and stirred until fully dissolved. The temperature is raised to 70 ℃ and the reaction is carried out for 72 hours. Cooling to room temperature, quenching the reaction with saturated sodium bicarbonate aqueous solution, extracting ethyl acetate until the aqueous phase has no fluorescent spots, combining all ethyl acetate phases, backwashing with saturated saline solution, drying with anhydrous sodium sulfate, filtering, and concentrating. The concentrate was purified by thin layer chromatography (petroleum ether/ethyl acetate=5:1) to give a mixture of compound 2-1 and compound 2-2 (yellow solid, 29.9mg, overall yield: 67%, ee% (enantiomeric excess): 51%,42%; dr (diastereomeric excess): 1:2)
The synthetic route is as follows:
HPLC conditions: INC column (n-hexane/isopropanol=95/5, flow rate 1.0 ml/min), retention time: compounds 2-1:t R =24.4 min (main), t R =50.7 min (times); compound 2-2: t is t R =15.0 min (times), t R =27.1 min (master).
Example 4
The synthesis method for asymmetrically synthesizing the 3, 3-disubstituted oxindole derivative comprises the following steps:
ligand L3 (6.4 mg,0.02 mmol) and Boc-D-phenylglycine (10 mg,0.04 mmol) were weighed into a 4mL reaction flask, anhydrous toluene (0.5 mL) was added, stirred for 10 minutes until fully dissolved, then 4-hexen-3-one (29.4 mg,0.3 mmol) was added to the reaction flask, stirred for 10 minutes until fully dissolved, then Compound 1 (35.6 mg,0.1 mmol) was weighed into the system and stirred until fully dissolved. The temperature is raised to 80 ℃ to react for 72 hours. Cooling to room temperature, quenching the reaction with saturated sodium bicarbonate aqueous solution, extracting ethyl acetate until the aqueous phase has no fluorescent spots, combining all ethyl acetate phases, backwashing with saturated saline solution, drying with anhydrous sodium sulfate, filtering, and concentrating. The concentrate was purified by thin layer chromatography (petroleum ether/ethyl acetate=5:1) to give a mixture of compound 2-1 and compound 2-2 (yellow solid, 30.3mg, total yield: 68%, ee% (enantiomeric excess): 64%,72%; dr (diastereomeric excess): 1:2)
The synthetic route is as follows:
HPLC conditions: INC column (n-hexane/isopropanol=95/5, flow rate 1.0 ml/min), retention time: compounds 2-1:t R =24.4 min (main), t R =50.7 min (times); compound 2-2: t is t R =15.0 min (times), t R =27.1 min (master).
Example 5
The synthesis method for asymmetrically synthesizing the 3, 3-disubstituted oxindole derivative comprises the following steps:
ligand L2 (6.4 mg,0.02 mmol) and Boc-D-phenylglycine (10 mg,0.04 mmol) were weighed into a 4mL reaction flask, anhydrous toluene (0.5 mL) was added, stirred for 10 minutes until fully dissolved, then 4-hexen-3-one (29.4 mg,0.3 mmol) was added to the reaction flask, stirred for 10 minutes until fully dissolved, then Compound 1 (35.6 mg,0.1 mmol) was weighed into the system and stirred until fully dissolved. The temperature is raised to 60 ℃ and the reaction is carried out for 72 hours. Cooling to room temperature, quenching the reaction with saturated sodium bicarbonate aqueous solution, extracting ethyl acetate until the aqueous phase has no fluorescent spots, combining all ethyl acetate phases, backwashing with saturated saline solution, drying with anhydrous sodium sulfate, filtering, and concentrating. The concentrate was purified by thin layer chromatography (petroleum ether/ethyl acetate=5:1) to give a mixture of compound 2-1 and compound 2-2 (yellow solid, 21.0mg, overall yield: 47%, ee% (enantiomeric excess): 55%,43%; dr (diastereomeric excess): 1:1.3)
The synthetic route is as follows:
HPLC conditions: INC column (n-hexane/isopropanol=95/5, flow rate 1.0 ml/min), retention time: compounds 2-1:t R =24.4 min (main), t R =50.7 min (times); compound 2-2: t is t R =15.0 min (times), t R =27.1 min (master).
Example 6
The synthesis method for asymmetrically synthesizing the 3, 3-disubstituted oxindole derivative comprises the following steps:
ligand L2 (6.4 mg,0.02 mmol) and Boc-D-phenylglycine (10 mg,0.04 mmol) were weighed into a 4mL reaction flask, anhydrous toluene (0.5 mL) was added, stirred for 10 minutes until fully dissolved, then 4-hexen-3-one (29.4 mg,0.3 mmol) was added to the reaction flask, stirred for 10 minutes until fully dissolved, then Compound 1 (35.6 mg,0.1 mmol) was weighed into the system and stirred until fully dissolved. The temperature is raised to 70 ℃ to react for 24 hours. Cooling to room temperature, quenching the reaction with saturated sodium bicarbonate aqueous solution, extracting ethyl acetate until the aqueous phase has no fluorescent spots, combining all ethyl acetate phases, backwashing with saturated saline solution, drying with anhydrous sodium sulfate, filtering, and concentrating. The concentrate was purified by thin layer chromatography (petroleum ether/ethyl acetate=5:1) to give a mixture of compound 2-1 and compound 2-2 (yellow solid, 14.3mg, overall yield: 32%, ee% (enantiomeric excess): 62%,49%; dr (diastereomeric excess): 1:1.8)
The synthetic route is as follows:
HPLC conditions: INC column (n-hexane/isopropanol=95/5, flow rate 1.0 ml/min), retention time: compounds 2-1:t R =24.4 min (main), t R =50.7 min (times); compound 2-2: t is t R =15.0 min (times), t R =27.1 min (master).
Example 7
The synthesis method for asymmetrically synthesizing the 3, 3-disubstituted oxindole derivative comprises the following steps:
ligand L2 (16.0 mg,0.05 mmol) and Boc-D-phenylglycine (25 mg,0.1 mmol) were weighed into a 4mL reaction flask, anhydrous toluene (0.5 mL) was added, stirred for 10 minutes until fully dissolved, then 4-hexen-3-one (29.4 mg,0.3 mmol) was added to the reaction flask, stirred for 10 minutes until fully dissolved, then Compound 1 (35.6 mg,0.1 mmol) was weighed into the system and stirred until fully dissolved. The temperature is raised to 70 ℃ and the reaction is carried out for 72 hours. Cooling to room temperature, quenching the reaction with saturated sodium bicarbonate aqueous solution, extracting ethyl acetate until the aqueous phase has no fluorescent spots, combining all ethyl acetate phases, backwashing with saturated saline solution, drying with anhydrous sodium sulfate, filtering, and concentrating. The concentrate was purified by thin layer chromatography (petroleum ether/ethyl acetate=5:1) to give a mixture of compound 2-1 and compound 2-2 (yellow solid, 39.3mg, total yield 88%, ee% (enantiomeric excess): 88%,92%; dr (diastereomeric excess): 1:1.8)
The synthetic route is as follows:
HPLC conditions: INC column (n-hexane/isopropanol=95/5, flow rate 1.0 ml/min), retention time: compounds 2-1:t R =24.4 min (main), t R =50.7 min (times); compound 2-2: t is t R =15.0 min (times), t R =27.1 min (master).
Example 8
The synthesis method for asymmetrically synthesizing the 3, 3-disubstituted oxindole derivative comprises the following steps:
ligand L2 (16.0 mg,0.05 mmol) and benzoic acid (12.2 mg,0.1 mmol) were weighed into a 4mL reaction flask, anhydrous toluene (0.5 mL) was added, stirred for 10 minutes to dissolve thoroughly, then 4-hexen-3-one (29.4 mg,0.3 mmol) was added to the reaction flask, stirred for 10 minutes to dissolve thoroughly, then Compound 1 (35.6 mg,0.1 mmol) was weighed into the system and stirred to dissolve completely. The temperature is raised to 70 ℃ and the reaction is carried out for 72 hours. Cooling to room temperature, quenching the reaction with saturated sodium bicarbonate aqueous solution, extracting ethyl acetate until the aqueous phase has no fluorescent spots, combining all ethyl acetate phases, backwashing with saturated saline solution, drying with anhydrous sodium sulfate, filtering, and concentrating. The concentrate was purified by thin layer chromatography (petroleum ether/ethyl acetate=5:1) to give a mixture of compound 2-1 and compound 2-2 (yellow solid, 41.5mg, overall yield: 93%, ee% (enantiomeric excess): 85%,83%; dr (diastereomeric excess): 1:1.8)
The synthetic route is as follows:
HPLC conditions: INC column (n-hexane/isopropanol=95/5, flow rate 1.0 ml/min), retention time: compounds 2-1:t R =24.4 min (main), t R =50.7 min (times); compound 2-2: t is t R =15.0 min (times), t R =27.1 min (master).
Example 9
The synthesis method for asymmetrically synthesizing the 3, 3-disubstituted oxindole derivative comprises the following steps:
ligand L2 (6.4 mg,0.02 mmol) and N-Boc-L-proline (10 mg,0.04 mmol) were weighed into a 4mL reaction flask, anhydrous toluene (0.5 mL) was added, stirred for 10 minutes to dissolve thoroughly, then 4-hexen-3-one (14.7 mg,0.15 mmol) was added to the reaction flask, stirred for 10 minutes to dissolve thoroughly, then Compound 1 (35.6 mg,0.1 mmol) was weighed into the system and stirred to dissolve completely. The temperature is raised to 70 ℃ and the reaction is carried out for 72 hours. Cooling to room temperature, quenching the reaction with saturated sodium bicarbonate aqueous solution, extracting ethyl acetate until the aqueous phase has no fluorescent spots, combining all ethyl acetate phases, backwashing with saturated saline solution, drying with anhydrous sodium sulfate, filtering, and concentrating. The concentrate was purified by thin layer chromatography (petroleum ether/ethyl acetate=5:1) to give a mixture of compound 2-1 and compound 2-2 (yellow solid, 11.6mg, total yield: 26%, ee% (enantiomeric excess): 81%,84%; dr (diastereomeric excess): 1:2)
The synthetic route is as follows:
HPLC conditions: INC column (n-hexane/isopropanol=95/5, flow rate 1.0 ml/min), retention time: compounds 2-1:t R =24.4 min (main), t R =50.7 min (times); compound 2-2: t is t R =15.0 min (times), t R =27.1 min (master).
The above examples 1-9 were synthesized to obtain a mixture of compound 2-1 and mixture 2-1, which was then subjected to a further conversion reaction to obtain compound 3-1 and compound 3-2, which were further isolated as follows:
a mixture of Compound 2-1 and Compound 2-2 (1.59 g,3.57 mmol) was weighed into a 100mL reaction flask, replaced with nitrogen, anhydrous dichloromethane (36 mL) was added, stirred until completely dissolved, and trifluoroacetic acid (88 mg,4.28 mmol) and trimethyloxonium tetrafluoroborate (1.58 g,10.7 mmol) were added; stirring for 6h at room temperature. The reaction was quenched with saturated aqueous sodium bicarbonate, extracted three times with ethyl acetate, the organic phases combined, backwashed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated. The concentrate was purified by column chromatography (petroleum ether/ethyl acetate=10:1) to give compound 3-1 (yellow oil, 905mg, yield: 54%), and compound 3-2 (yellow oil, 504mg, yield: 30%).
The structural formula of the compound 3-1 isCompound 3-2 has the structural formula +.>
The structures of all the compounds in examples 1 to 9 above were confirmed by nuclear magnetic resonance spectroscopy, and fig. 1 is a hydrogen spectrum of compound 1; FIG. 2 is a carbon spectrum of Compound 1; FIG. 3 is a hydrogen spectrum of compound 2-1 and compound 2-2; FIG. 4 is a hydrogen spectrum of Compound 3-1; FIG. 5 is a hydrogen spectrum of Compound 3-2. The authentication data are as follows:
compound 1:
1 H NMR(500MHz,CDCl3)δ8.71(s,1H),7.35-7.25(m,8H),7.25-7.18(m,2H),7.11(t,J＝7.7Hz,1H),6.84-6.77(m,2H),6.60(d,J＝7.3Hz,1H),3.72(d,J＝13.5Hz,2H),3.58(dd,J＝8.0,4.9Hz,1H),3.47(d,J＝13.5Hz,2H),2.75-2.67(m,1H),2.67-2.59(m,1H),2.35-2.26(m,1H),1.97-1.86(m,1H).
13 C NMR(125MHz,CDCl3)δ180.8,141.5,139.5,130.0,129.2,128.4,127.7,127.0,124.3,122.2,109.7,58.4,50.2,43.8,28.7.
compound 2-1 and compound 2-2:
1 H NMR(400MHz,Chloroform-d)δ8.22(s,0.52H),8.17(s,0.28H),8.14-8.08(m,0.55H),7.58(d,J＝7.4Hz,0.28H),7.47(t,J＝7.7Hz,0.55H),7.36-7.29(m,0.55H),7.29-7.07(m,10.88H),7.01-6.85(m,1.91H),6.82(d,J＝7.7Hz,0.20H),6.78(d,J＝7.8Hz,0.92H),3.73(d,J＝13.5Hz,0.28H),3.61(dd,J＝14.7,8.4Hz,0.3H),3.55-3.35(m,4H),2.59-2.46(m,1.22H),2.39-2.07(m,5.81H),2.02-1.91(m,1.05H),1.00(t,J＝7.3Hz,0.95H),0.95(t,J＝7.3Hz,1.85H),0.87(d,J＝6.7Hz,2.02H),0.74(d,J＝6.7Hz,0.94H).
compound 3-1:
1 H NMR(500MHz,CDCl 3 )δ7.28-7.19(m,12H),7.01-6.91(m,2H),3.84(s,3H),3.51-3.40(m,4H),2.53-2.49(m,1H),2.27-2.20(m,2H),2.19-2.11(m,2H),2.09-2.01(m,3H),1.86-1.83(m,1H),0.96(t,J＝7.4Hz,3H),0.69(d,J＝6.7Hz,3H).
compound 3-2:
1 H NMR(500MHz,Chloroform-d)δ7.29-7.18(m,12H),7.06-6.97(m,2H),3.78(s,3H),3.56-3.32(m,4H),2.57-2.48(m,1H),2.32-2.15(m,3H),2.08-1.95(m,4H),1.88-1.80(m,1H),0.96(q,J＝7.3Hz,3H),0.87(d,J＝6.8Hz,3H).
the above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications that do not depart from the spirit and principle of the present invention should be made in the equivalent manner, and the embodiments are included in the protection scope of the present invention.
Claims (10)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311649212.8A CN117777002A (en) | 2023-12-04 | 2023-12-04 | An asymmetric synthesis method of 3,3-disubstituted oxyindole derivatives |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311649212.8A CN117777002A (en) | 2023-12-04 | 2023-12-04 | An asymmetric synthesis method of 3,3-disubstituted oxyindole derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN117777002A true CN117777002A (en) | 2024-03-29 |
Family
ID=90380590
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202311649212.8A Pending CN117777002A (en) | 2023-12-04 | 2023-12-04 | An asymmetric synthesis method of 3,3-disubstituted oxyindole derivatives |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN117777002A (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1117727A (en) * | 1993-02-17 | 1996-02-28 | 中外制药株式会社 | Indolin-2-one derivatives |
| CN101213174A (en) * | 2005-04-20 | 2008-07-02 | 泽农医药公司 | Oxindole compounds and their use as therapeutic agents |
| CN102382031A (en) * | 2011-08-16 | 2012-03-21 | 河北博伦特药业有限公司 | 3 - substituted allylic ester oxindole and preparation method thereof |
-
2023
- 2023-12-04 CN CN202311649212.8A patent/CN117777002A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1117727A (en) * | 1993-02-17 | 1996-02-28 | 中外制药株式会社 | Indolin-2-one derivatives |
| CN101213174A (en) * | 2005-04-20 | 2008-07-02 | 泽农医药公司 | Oxindole compounds and their use as therapeutic agents |
| CN102382031A (en) * | 2011-08-16 | 2012-03-21 | 河北博伦特药业有限公司 | 3 - substituted allylic ester oxindole and preparation method thereof |
Non-Patent Citations (3)
| Title |
|---|
| RUI YANG ET AL.: ""Asymmetric Synthesis of Arboduridine"", 《ANGEW. CHEM. INT. ED.》, vol. 63, 15 December 2023 (2023-12-15), pages 202316016 * |
| WANGSHENG SUN ET AL.: ""Asymmetric construction of quaternary stereocenters by direct conjugate addition of oxindoles to enone"", 《TETRAHEDRON: ASYMMETRY》, vol. 21, 2 November 2010 (2010-11-02), pages 2493 - 2497 * |
| YUAN WEI ET AL.: ""Diastereodivergent Catalytic Asymmetric Michael Addition of 2‑Oxindoles to α, β-Unsaturated Ketones by Chiral Diamine Catalysts"", 《ORG. LETT.》, vol. 17, 14 May 2015 (2015-05-14), pages 2732 - 2735 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| WO2022050234A1 (en) | Method for producing formic acid salt, method for producing formic acid, catalyst for producing formic acid salt, and ruthenium complex | |
| CN119143755B (en) | A method for preparing racemic mixtures from enantiomeric phenelzine or its intermediates | |
| CN113880750A (en) | Synthesis method of chiral 3-substituted-3-aryl oxindole compound | |
| CN102659662A (en) | A synthetic method of 3-R-3-hydroxy-2-oxindole compound | |
| WO2007013698A1 (en) | Process for production of mono-substituted alkylated compound using aldimine or derivative thereof | |
| CN114716361B (en) | Method for synthesizing chiral spiro indenone-pyrrole compound | |
| CN117777002A (en) | An asymmetric synthesis method of 3,3-disubstituted oxyindole derivatives | |
| KR20250166841A (en) | Method for synthesizing and separating chiral 3-hydroxy-4-fluoropiperidine derivatives | |
| Łowicki et al. | Stereoselective protonation of 2-methyl-1-tetralone lithium enolate catalyzed by salan-type diamines | |
| CN112358457B (en) | A kind of method of synthesizing chiral bridged cyclic lactone | |
| CN118666838B (en) | Asymmetric synthesis method of 1, 1-disubstituted-tetrahydro-beta-carboline derivative | |
| CN112409235B (en) | Chiral 4-halogenated tryptophan derivative and synthetic method thereof | |
| CN111662147B (en) | Process for preparing diynes and analogues thereof | |
| CN116283937B (en) | A method for photocatalytic synthesis of aromatic secondary amine compounds | |
| CN114160206B (en) | Catalyst for catalytic synthesis of optically active indole compound, application and synthesis method thereof, and optically active indole compound | |
| CN119080676B (en) | A method for synthesizing polycyclic indole compounds by photocatalytic cycloaddition reaction | |
| CN119350351B (en) | A nitrogen-centered chiral Tröger base derivative, its preparation method and application | |
| CN119409583B (en) | A β-chiral tertiary amine compound and its preparation method | |
| CN121181461A (en) | A method for synthesizing 1-benzyl-4-[3-(benzyloxy)propyl]-1,3-dihydro-2H-pyrrole-2-one | |
| CN116283527B (en) | A method for synthesizing a tetrahydronaphthalene ketone skeleton with high enantioselectivity | |
| CN113121543B (en) | A kind of preparation method of azepano[4,5-b]indole compound | |
| CN117683016A (en) | Synthesis of Chiral 3,4-Disubstituted Aminopyridine Catalyst and Its Application in Black Rearrangement | |
| CN121779199A (en) | A method for preparing 1-benzyl alcohol-3-alkylbicyclo[1.1.1]pentane | |
| CN119431242A (en) | A chiral 2-azabicyclo[3.1.1]heptane derivative and a synthesis method thereof | |
| CN119431252A (en) | A 2,3-diazabicyclo[3.1.1]heptane derivative and a synthesis method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |